Su Qian, Chen Li, Liu Dong, Xu Yanzhen, Feng Jinxing, Yu Jialin, Zhang Zhaoxia, Yu Zhangbin
Department of Neonatology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, China.
Department of Neonatology, Shenzhen Children's Hospital, Shenzhen, 518020, Guangdong, China.
Pediatr Surg Int. 2025 Jan 8;41(1):61. doi: 10.1007/s00383-025-05963-6.
This study aims to elucidate the roles of the PI3K-Akt signaling pathway and enterocyte apoptosis in necrotizing enterocolitis (NEC) pathogenesis and investigate the impact of vitamin A intervention on these factors.
We employed an NEC mouse model and administered vitamin A treatment. Retinol levels in mouse blood were quantified using ELISA. Intestinal cell apoptosis in NEC mice was assessed via the TUNEL assay. We evaluated mRNA and protein expressions of Bcl-2, Bax, cytochrome C (CytoC), Caspase 3, and PI3K/Akt signaling pathway components using qPCR and western blotting.
In NEC models, PI3K, Akt, and Bcl-2 were downregulated, accompanied by upregulated Bax, CytoC, and Caspase 3 at both mRNA and protein levels. These molecular changes were associated with an increase in enterocyte apoptosis in the NEC models. Vitamin A supplementation increased PI3K, Akt, and Bcl-2 expression while decreasing Bax, CytoC, and Caspase 3 levels in the NEC models, resulting in reduced apoptosis.
Vitamin A has the potential to mitigate enterocyte apoptosis in NEC by upregulating the PI3K/Akt signaling pathway and modulating apoptotic signals, providing new insights into the inhibitory effect of vitamin A on enterocyte apoptosis in NEC.
本研究旨在阐明PI3K-Akt信号通路和肠上皮细胞凋亡在坏死性小肠结肠炎（NEC）发病机制中的作用，并研究维生素A干预对这些因素的影响。
我们采用NEC小鼠模型并给予维生素A治疗。使用酶联免疫吸附测定（ELISA）定量小鼠血液中的视黄醇水平。通过TUNEL测定评估NEC小鼠的肠细胞凋亡。我们使用实时定量聚合酶链反应（qPCR）和蛋白质免疫印迹法评估Bcl-2、Bax、细胞色素C（CytoC）、半胱天冬酶3（Caspase 3）以及PI3K/Akt信号通路成分的mRNA和蛋白质表达。
在NEC模型中，PI3K、Akt和Bcl-2在mRNA和蛋白质水平均下调，同时Bax、CytoC和Caspase 3上调。这些分子变化与NEC模型中肠上皮细胞凋亡增加相关。在NEC模型中补充维生素A可增加PI3K、Akt和Bcl-2的表达，同时降低Bax、CytoC和Caspase 3的水平，从而减少细胞凋亡。
维生素A有可能通过上调PI3K/Akt信号通路和调节凋亡信号来减轻NEC中的肠上皮细胞凋亡，为维生素A对NEC中肠上皮细胞凋亡的抑制作用提供了新的见解。
